Combination gefitinib and methotrexate compared with methotrexate alone to treat ectopic pregnancy.

Abstract

OBJECTIVE:

To determine the safety, tolerability, and efficacy of combination gefitinib and methotrexate to treat ectopic pregnancy.

METHODS:

We performed a phase I, single-arm (nonrandomized), open-label study. Twelve women with ectopic pregnancies were administered methotrexate (50 mg/m, intramuscular) and 250 mg oral gefitinib in a dose-escalation protocol: one dose (day 1) n=3; three doses (days 1-3) n=3; seven doses (days 1-7) n=6. Efficacy was examined by comparing human chorionic gonadotrophin (hCG) decline and time to resolution with historic controls administered methotrexate only.

RESULTS:

Common side effects were transient acneiform rash in 67% (8/12) and diarrhea in 42% (5/12) of participants. There was no clinical or biochemical evidence of serious pulmonary, renal, hepatic, or hematologic toxicity. Of six participants with a pretreatment serum hCG level between 1,000 and 3,000 international units/L, hCG levels declined significantly faster than in the control group. Median serum hCG levels by day 7 after treatment were less than one fifth of levels observed among 71 historic controls treated with methotrexate alone (median [interquartile range] hCG in participants 261 [55-1,445] international units/L compared with controls 1,426 [940-2,573]; P=.008). Median time for the ectopic pregnancies to resolve with combination therapy was 34% shorter compared with methotrexate alone (21 days compared with 32 days; P=.018).

CONCLUSION:

Combination gefitinib and methotrexate has potential as a treatment for ectopic pregnancy but is commonly associated with minor side effects such as transient rash and diarrhea. The treatment requires validation of safety and efficacy in a larger trial.

CLINICAL TRIAL REGISTRATION:

Australian New Zealand Clinical Trials Registry, www.anzctr.org, AC'TRN12610000684022.

LEVEL OF EVIDENCE:

: II.

• Authors: Monika M Skubisz, Andrew W Horne, Terrance G Johns, Ulrika W Nilsson, W Colin Duncan, Euan M Wallace, Hilary O D Critchley, Stephen Tong
• Journal: Obstetrics and gynecology (Obstet Gynecol) Vol. 122 Issue 4 Pg. 745-751 (Oct 2013) ISSN: 1873-233X [Electronic] United States
• PMID: 24084530 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Abortifacient Agents, Nonsteroidal
• Antineoplastic Agents
• Quinazolines
• Gefitinib
• Methotrexate

Topics

• Abortifacient Agents, Nonsteroidal (therapeutic use)
• Adult
• Antineoplastic Agents (therapeutic use)
• Drug Therapy, Combination
• Female
• Gefitinib
• Humans
• Injections, Intramuscular
• Methotrexate (therapeutic use)
• Pregnancy
• Pregnancy, Ectopic (drug therapy)
• Quinazolines (therapeutic use)